Background and Objective Whether and when surgical intervention is indicated for mediastinal cysts is a matter of some debate. While most mediastinal cysts are found incidentally, the anatomic location, clinical presentation, and symptoms, as well as the potential for malignancy, are important considerations that inform decisions related to whether to intervene surgically. The objective of this review is to summarize the current literature regarding the criteria for surgical excision of mediastinal cysts and provide a framework for the clinician and surgeon to arrive at a decision regarding the appropriateness of surgical intervention of mediastinal cysts. Methods A review of the published literature in the last 45 years (1977–2022) was conducted through PubMed, MeSh and Google Scholar. We included retrospective reviews, meta-analyses, and case studies published in the English language. A single author identified eligible studies, and those identified were reviewed by the team until consensus was met. Pediatric literature was excluded from this review. Key Content and Findings The current literature predominantly contains case studies, small retrospective studies, and meta-analyses describing mediastinal cysts. In the anterior mediastinum, multiloculated thymic cysts should be resected to rule out thymic malignancy. Intralesional fat, smooth borders, and a more midline location are features suggestive of a benign process, while asymmetric cystic wall thickening has been associated with malignancy. Both esophageal and bronchogenic cysts should be excised, taking into account the risk of complications (up to a 45% risk) of infection, rupture, or compression, as well as the rare risk of associated malignancy. Simple thymic and small pericardial cysts can be observed and followed with serial radiographic tools and should be resected if they increase in size, compress surrounding structures, or lead the patient to develop symptoms. Conclusions Since mediastinal cysts are rare and often asymptomatic, there are no formal guidelines outlining when surgical intervention should be undertaken. Based on our review of the literature, surgical intervention should be pursued if the patient’s symptoms correlate with radiographic findings of a mediastinal cyst, there is compression of the surrounding structures, and concern of malignancy is present.
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